, Volume 13, Issue 2, pp 314-320
Date: 18 Jun 2010

MRI with Magnetic Nanoparticles Monitors Downstream Anti-Angiogenic Effects of mTOR Inhibition

Rent the article at a discount

Rent now

* Final gross prices may vary according to local VAT.

Get Access

Abstract

Purpose

To study the effect of mammalian target of rapamycin (mTOR) inhibition on angiogenesis with magnetic resonance imaging (MRI) using magnetic iron oxide nanoparticles (MNP).

Procedures

One million CAK-1 renal cell carcinoma cells were subcutaneously implanted into each of 20 nude mice. When tumors reached ∼750 μl, four daily treatment arms began and continued for 4 weeks: rapamycin (mTOR inhibitor) 10 mg/kg/day; sorafenib (VEGF inhibitor) high dose (80 mg/kg/day) and low dose (30 mg/kg/day); and saline control. Weekly MRI (4.7 T Bruker Pharmascan) was performed before and after IV MION-48, a prototype MNP similar to MNP in clinical trials. Vascular volume fraction (VVF) was quantified as ΔR2 (from multi-contrast T2 sequences) and normalized to assumed muscle VVF of 3%. Linear regression compared VVF to microvascular density (MVD) as determined by histology.

Results

VVF correlated with MVD (R2 = 0.95). VVF in all treatment arms differed from control (p < 0.05) and declined weekly with treatment. VVF changes with rapamycin were similar to high-dose sorafenib.

Conclusion

This study demonstrates noninvasive, in vivo anti-angiogenic monitoring using MRI of mTOR inhibition.